A common antibiotic used to treat skin and lung infections may prolong the lives and ease the symptoms of patients with Lou Gehrig's disease and other neurological ailments, according to Johns Hopkins researchers.
Scientists from the Hopkins medical school reported in the journal Nature this week that injections of ceftriaxone increased survival rates of mice genetically engineered with Lou Gehrig's disease, known scientifically as amyotrophic lateral sclerosis, or ALS.
The prescription drug also delayed the nerve damage and loss of muscle function that are common symptoms of ALS.
Although results with laboratory animals are often difficult to duplicate in humans, the findings indicate that ceftriaxone contains some ingredient with the potential to treat not only ALS, but also other neurological disorders, including dementia and epilepsy, the researchers say.
"What it means is, there's a whole class of drugs out there that we may be able to use in new ways," said Dr. Jeffrey Rothstein, lead author of the paper.
The study is part of a nationwide research effort launched two years ago by the National Institutes of Health to see if existing drugs can be used for new purposes.
Rothstein said he chose ceftriaxone, sold under the brand name Rocephin, because it's part of a class of antibiotics called beta-lactams and is known to generate chemical activity in the brain. He said there may be other antibiotics, yet to be tested, that are even more effective.
A national clinical trial of ceftriaxone, involving hundreds of ALS patients, is planned to begin in the spring.
"We have to continue working on this. If we stopped now it would be stupid," he said.
Rothstein and Hopkins hold patents on beta-lactams as drugs that protect nerves from damage. But Rothstein said that if the drug is developed into a viable treatment for ALS and other neurological disorders, the proceeds from the patents will go to Hopkins and he will request that the school invest it in ALS research.
"I put the patent applications in mainly to ensure that the research can continue," he said.
ALS is caused by a destruction of cells that relay messages from the brain to muscles in the body. It afflicts 20,000 to 30,000 people in the United States, kills 5,000 each year and got its popular name from Lou Gehrig, the famed New York Yankees first baseman who died of the disease in 1941.
Most victims first experience weakness in the arms and legs and ultimately become unable to move, speak or swallow. Death usually occurs within two to four years of the onset of symptoms.
Finding a cause and a cure for ALS and other neurological disorders has proved difficult, in large part because the nerve cells where they originate are still largely a mystery, experts say.
"We're really only beginning to understand the basics of a nerve cell. What it is, how it works," said Dr. Robert Brown, an expert on Lou Gehrig's disease who directs a neuromuscular research lab at Massachusetts General Hospital.
But researchers have known for decades that glutamate - a chemical that excites nerve cells and sends messages that control body movements - plays a key role in the disease.
In the 1980s, Rothstein discovered that too much glutamate has a toxic effect on nerve cells and that ALS patients had elevated levels of it.
When NIH moved to find new uses for existing drugs, Rothstein said he decided to focus on an antibiotic that might affect glutamate levels in the brain.
The study found that ceftriaxone activates a protein known as GLT1 that serves as a transporter in the brain's nerve cells. By activating the protein, the antibiotic increased the number of pathways used to remove glutamate, reducing nerve damage caused by excessive amounts of glutamate.
At least 60 mice were tested as part of the study, Rothstein said. The treated mice survived an average of 10 days longer than untreated mice and effects of the drug lasted for up to three months after treatment, the study showed.
The results surprised some experts - in part because antibiotics are normally used to clear up infections caused by bacteria. But many cautioned that further studies are needed and that it will be a long time before physicians start prescribing antibiotics for neurological disorders.
"It's a breakthrough in that they're using an old drug to treat a new target. But whether this drug will be effective in treating humans remains to be seen," said Dr. Marinos Dalakas, chief of the neuromuscular disease section at the National Institute of Neurological Disorders and Stroke.
Rothstein is equally cautious. He said the best test for determining ceftriaxone's effectiveness will be the national clinical trials that will begin in the spring.
He also warned against taking antibiotics for extended periods because of concerns that long-term use can have toxic effects and spawn disease-resistant bacteria.
"How well a given drug will work on any given disease, no one knows," he said.